Roxadustat markedly reduces myocardial ischemia reperfusion injury in mice

Hiroko Deguchi, Masataka Ikeda, Tomomi Ide, Tomonori Tadokoro, Soichiro Ikeda, Kosuke Okabe, Akihito Ishikita, Keita Saku, Shouji Matsushima, Hiroyuki Tsutsui

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Abstract

Background: Ischemic preconditioning (IPC) is an effective procedure to protect against ischemia/reperfusion (I/R) injury. Hypoxia-inducible factor-1α (Hif-1α) is a key molecule in IPC, and roxadustat (RXD), a first-in-class prolyl hydroxylase domain-containing protein inhibitor, has been recently developed to treat anemia in patients with chronic kidney disease. Thus, we investigated whether RXD pretreatment protects against I/R injury. Methods and Results: RXD pretreatment markedly reduced the infarct size and suppressed plasma creatinine kinase activity in a murine I/R model. Analysis of oxygen metabolism showed that RXD could produce ischemic tolerance by shifting metabolism from aerobic to anaerobic respiration. Conclusions: RXD pretreatment may be a novel strategy against I/R injury.

Original languageEnglish
Pages (from-to)1028-1033
Number of pages6
JournalCirculation Journal
Volume84
Issue number6
DOIs
Publication statusPublished - 2020

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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